Currently between 50-75 million Americans have metabolic or insulin resistance syndrome. A convincing body of scientific evidence indicates that the ingestion of w6 and w3 PUFAs plays an important role in the prevention or induction of numerous inflammatory disorders including metabolic syndrome/diabetes. Our preliminary data suggests that there are major genetic differences in poly-unsaturated (PUFA) metabolism in different individuals and racial groups. Furthermore, our preliminary data and the work of others show that certain alleles in the fatty acid desaturase (FADS) gene cluster on chromosome 11q12-q13 are associated with higher levels of PUFA metabolism and may place certain individuals or racial groups at higher risk of certain inflammatory diseases. We hypothesize that single nucleotide polymorphisms (SNPs) in this region will also be associated with the capacity of MC-PUFA-based botanical supplements to impact inflammatory disease. With this as a background, the overall goal of this proposal is to provide a better understanding of gene-nutrient interactions with regard to PUFA metabolism and and their role in the effectiveness of botanical PUFA-based dietary supplements. Aim 1 investigates the association of SNPs in FADS with medium and long chain w3 and w6 PUFA levels and ratios in African Americans and Caucasians with and without metabolic syndrome/diabetes. Subaims will determine how different genotypes in a locus that tracks closely with FADS1 activity affects the expression of gene mRNA transcripts and protein levels in leukocytes as well as immune cell functional responses(eicosanoid generation by basophils, neutrophils and whole blood;inflammatory gene expression in circulating mononuclear cells). In Aim 2, we will investigate how genotypes in this same SNP affects the metabolism of PUFAs in botanical supplements and impacts the capacity of botanical supplements to reduce indices of inflammation in metabolic syndrome/diabetic subjects. The long term-objective of this research is to gain the understanding to optimize the response of individuals and groups to PUFA-based botanical supplements using a rational nutrient-gene based strategy. This could ultimately lead to MC-PUFA botanical supplemnts that would specifically optimize the health of individuals.